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https://www.readbyqxmd.com/read/29351467/from-ionic-to-cellular-variability-in-human-atrial-myocytes-an-integrative-computational-and-experimental-study
#1
Anna Muszkiewicz, Xing Liu, Alfonso Bueno-Orovio, Brodie A J Lawson, Kevin Burrage, Barbara Casadei, Blanca Rodriguez
Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and sub-cellular ionic densities on calcium transient dynamics...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351452/the-role-of-intracellular-angiotensin-ii
#2
Richard N Re
It has become clear that the vasoactive peptide angiotensin II, like other so-called intracrines, can act in the intracellular space. Evidence has accumulated indicating that such angiotensin II activity can be upregulated in disease states and cause pathology. Indeed, other intracrines appear to be involved in disease pathogenesis as well. At the same time nitric oxide, potentially a cell protective factor, has been shown to be upregulated by intracellular angiotensin II. Recently data has been developed indicating that other potentially protective factors are directly upregulated at neuronal nuclei by angiotensin II...
January 12, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351417/zinc-regulates-vascular-endothelial-activities-through-zinc-sensing-receptor-znr-gpr39
#3
Donghui Zhu, Yingchao Su, Yufeng Zheng, Bingmei M Fu, Liping Tang, Yi-Xian Qin
Zn2+ is an essential element for cell survival/growth, and its deficiency is linked to many disorders. Extracellular Zn2+ concentration changes participate in modulating fundamental cellular processes such as proliferation, secretion, ion transport, and cell signal transduction in a mechanism that is not well understood. Here, we hypothesize that the Zn-sensing receptor ZnR/GPR39, found in tissues where dynamic Zn2+ homeostasis takes place, enables extracellular Zn2+ to trigger intracellular signaling pathways regulating key cell functions in vascular cells...
December 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351414/the-murine-choroid-plexus-epithelium-expresses-the-2cl-h-exchanger-clc-7-and-na-h-exchanger-nhe6-in-the-luminal-membrane-domain
#4
Helle H Damkier, Henriette L Christensen, Inga B Christensen, Qi Wu, Robert A Fenton, Jeppe Praetorius
The choroid plexus epithelium within the brain ventricles secretes the majority of the cerebrospinal fluid (CSF). The luminal Na+,K+-ATPase acts in concert with a host of other transport proteins to mediate efficient fluid secretion across the epithelium. The CSF contains little protein buffer, but the pH value seems nonetheless maintained within narrow limits, even when faced with acid/base challenges. The involvement of choroid plexus acid/base transporters in CSF pH regulation is highlighted by the expression of several acid/base transporters in the epithelium...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351411/disruption-of-the-lens-circulation-causes-calcium-accumulation-and-precipitates-in-connexin-mutant-mice
#5
Junyuan Gao, Peter J Minogue, Eric C Beyer, Richard T Mathias, Viviana M Berthoud
The lens is an avascular organ whose function and survival depend on an internal circulation system. Cx46fs380 mice model a human autosomal dominant cataract caused by a mutant lens connexin. In these mice, fiber cell connexin levels and gap junction coupling are severely decreased. The present studies were conducted to examine components of the lens circulation system that might be altered and contribute to the pathogenesis of cataracts. Lenses from wild type mice and Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351409/pharmacological-activation-of-ppar%C3%AE-inhibits-hypoxia-induced-proliferation-through-a-caveolin-1-targeted-and-dependent-mechanism-in-pasmcs
#6
Kai Yang, Mingming Zhao, Junyi Huang, Chenting Zhang, Qiu Yu Zheng, Yuqin Chen, Haiyang Jiang, Wenju Lu, Jian Wang
Previously, we and others have demonstrated that activation of peroxisome proliferator- activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351189/the-role-of-cadaverine-synthesis-on-pneumococcal-capsule-and-protein-expression
#7
Mary F Nakamya, Moses B Ayoola, Seongbin Park, Leslie A Shack, Edwin Swiatlo, Bindu Nanduri
Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation...
January 19, 2018: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29350596/enhancement-of-antitumor-activity-by-using-5-ala-mediated-sonodynamic-therapy-to-induce-apoptosis-in-malignant-gliomas-significance-of-high-intensity-focused-ultrasound-on-5-ala-sdt-in-a-mouse-glioma-model
#8
Satoshi Suehiro, Takanori Ohnishi, Daisuke Yamashita, Shohei Kohno, Akihiro Inoue, Masahiro Nishikawa, Shiro Ohue, Junya Tanaka, Takeharu Kunieda
OBJECTIVE High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells...
January 19, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29350547/regulation-of-autophagy-by-hepatitis-c-virus-for-its-replication
#9
Linya Wang, Jing-Hsiung James Ou
Macroautophagy, hereafter autophagy, is a catabolic process that is important for maintaining cellular homeostasis. It can also be used by cells to remove intracellular microbial pathogens. However, the studies on hepatitis C virus (HCV) in recent years indicated that this virus could regulate this cellular pathway and use it to enhance its replication. HCV could temporally control the autophagic flux and use the autophagic membranes for the assembly of its RNA replication complex. In this report, we will discuss the biogenesis of autophagosomes induced by HCV and how HCV uses this autophagic pathway for its RNA replication...
January 19, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#10
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29350381/macrophage-migration-inhibitory-factor-knockout-attenuates-endotoxin-induced-cardiac-dysfunction-in-mice
#11
Jie Zhang, Xin Zhang, Yuqi Cui, Lianqun Cui, Peng Zhao
BACKGROUND: The accumulated evidence suggests that macrophage migration inhibitory factor (MIF) plays a key role not only in acute and chronic inflammatory diseases but also in cardiovascular disease. The cardiac dysfunction is related to lipopolysaccharide (LPS) in sepsis. AIM: This study was designed to examine whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms. METHODS: Echocardiography, immunohistochemical analysis, cell shortening/relengthening and intracellular Ca2+ fluorescence evaluation were performed in whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated with or without LPS...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29350302/antifungal-mechanism-of-sodium-dehydroacetate-against-geotrichum-citri-aurantii
#12
Xu Tang, Qiuli Ouyang, Guoxing Jing, Xingfeng Shao, Nengguo Tao
This study investigated the potential anti-fungal mechanisms of sodium dehydroacetate (SD) against Geotrichum citri-aurantii. The results showed that the cell wall integrity of G. citri-aurantii was not affected, whereas the membrane permeability of G. citri-aurantii mycelia was visibly altered by SD. Dramatic morphological changes of the mycelia, such as loss of cytoplasm, plasmolysis, and dissolution of intracellular substances, were observed by scanning electron microscopy and transmission electron microscopy analyses, indicating that the mycelium is severely damaged by the SD treatment...
January 19, 2018: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29350268/the-epitope-mediated-mmp-activation-assay-detection-and-quantification-of-the-activation-of-mmp2-in-vivo-in-the-zebrafish-embryo
#13
Emma J Jeffrey, Bryan D Crawford
Matrix remodeling is a consequence of tightly regulated matrix metalloproteinase (MMP) activity. MMPs are synthesized as inactive precursors with auto-inhibitory N-terminal propeptides, the proteolytic removal of which exposes the catalytic zinc ion, rendering the protease active. The regulation of MMP activation has been investigated primarily in tissue culture and biochemical assays that lack important biological context. Here we present the epitope-mediated MMP activation (EMMA) assay and use it to observe the activation of Mmp2 (gelatinase A) by endogenous mechanisms in the intact zebrafish embryo...
January 19, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29350155/yersinia-pestis-survival-and-replication-in-potential-ameba-reservoir
#14
David W Markman, Michael F Antolin, Richard A Bowen, William H Wheat, Michael Woods, Mercedes Gonzalez-Juarrero, Mary Jackson
Plague ecology is characterized by sporadic epizootics, then periods of dormancy. Building evidence suggests environmentally ubiquitous amebae act as feral macrophages and hosts to many intracellular pathogens. We conducted environmental genetic surveys and laboratory co-culture infection experiments to assess whether plague bacteria were resistant to digestion by 5 environmental ameba species. First, we demonstrated that Yersinia pestis is resistant or transiently resistant to various ameba species. Second, we showed that Y...
February 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29349918/dual-drug-backboned-shattering-polymeric-theranostic-nanomedicine-for-synergistic-eradication-of-patient-derived-lung-cancer
#15
Yuwei Cong, Haihua Xiao, Hejian Xiong, Zigui Wang, Jianxun Ding, Chan Li, Xuesi Chen, Xing-Jie Liang, Dongfang Zhou, Yubin Huang
Most of the current nanoparticle-based therapeutics worldwide failing in clinical trials face three major challenges: (i) lack of an optimum drug delivery platform with precise composition, (ii) lack of a method of directly monitoring the fate of a specific drug rather than using any other labelling molecules as a compromise, and (iii) lack of reliable cancer models with high fidelity for drug screen and evaluation. Here, starting from a PP2A inhibitor demethylcantharidin (DMC) and cisplatin, the design of a dual sensitive dual drug backboned shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for precise nanomedicine is shown...
January 19, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29349894/assessment-of-the-potential-of-temporin-peptides-from-the-frog-rana-temporaria-ranidae-as-anti-diabetic-agents
#16
Vishal Musale, Bruno Casciaro, Maria Luisa Mangoni, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon
Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana temporaria, produced concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active...
January 19, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29349780/protective-effect-of-bled-exposed-conditioned-media-on-cell-injury
#17
Phil-Sun Oh, Eun-Mi Kim, Minjoo Kim, In Sun Kim, Yeon-Hee Han, SeokTae Lim, Myung-Hee Sohn, Myoung-Hwan Ko, Hwan-Jeong Jeong
Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. The present study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis...
January 19, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29349707/piperazine-clubbed-with-2-azetidinone-derivatives-suppresses-proliferation-migration-and-induces-apoptosis-in-human-cervical-cancer-hela-cells-through-oxidative-stress-mediated-intrinsic-mitochondrial-pathway
#18
Rashmin Khanam, Raj Kumar, Iram Iqbal Hejazi, Syed Shahabuddin, Ramovatar Meena, Vikrant Jayant, Prabhat Kumar, Abdul Roouf Bhat, Fareeda Athar
Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis...
January 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#19
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349568/class-iii-bacteriocin-helveticin-m-causes-sublethal-damage-on-target-cells-through-impairment-of-cell-wall-and-membrane
#20
Zhilan Sun, Xiaomeng Wang, Xinxiao Zhang, Haihong Wu, Ye Zou, Pengpeng Li, Chong Sun, Weimin Xu, Fang Liu, Daoying Wang
Helveticin-M, a novel Class III bacteriocin produced by Lactobacillus crispatus exhibited an antimicrobial activity against Staphylococcus aureus, S. saprophyticus, and Enterobacter cloacae. To understand how Helveticin-M injured target cells, Helveticin-M was cloned and heterologously expressed in Escherichia coli. Subsequently, the cell wall organization and cell membrane integrity of target cells were determined. The mechanism of cellular damage differed according to bacterial species. Based on morphology analysis, Helveticin-M disrupted the cell wall of Gram-positive bacteria and disorganized the outer membrane of Gram-negative bacteria, therefore, altering surface structure...
January 18, 2018: Journal of Industrial Microbiology & Biotechnology
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